New butene derivative and their preparation



NEW BIQJTENE DERIVATIVE AND THEIR PREPARATION Herbert Schwartz,Vineland, N. J., assignor to Vineland' Chemical Company, Vineland, N.J., a firm.

No Drawing. ApplicationMar'ch 29,1956

Serial No. 574,611 r w 7 Claims. 01. 260-437) This invention relates tonovel chemical compounds which are valuable pesticides or pest controlagents, and I more particularly to new 1,4-substituted Z-butenederivatives possessing valuable fungicidal, germicidal and herbicidalproperties. The term pesticide as employed herein means a chemicalcompound or substance for combating and destroying pests such as fungi,bacteria or'germs, noxious grass or weeds, and like pests.

It is the principal object of this invention to provide new chemicalcompounds that properties.

Another object of this invention is to provide new possess valuablepesticidal' chemical compounds that possess valuable-fungicidal,

germicidal and herbicidal properties. i

Still another object of this invention is to provide new chemicalcompounds which exhibit valuable systemic fungicidal activity in growingplants. 1

Further objects, including the provision of a method for making thenovel compounds, will become apparent from a consideration of thefollowing specification and claims.

The novel chemical compounds of thepresent invention are 1,4-substitutedZ-butene derivatives having the general structural formula:

wherein X represents a substituent selected from the.

group consisting of hydroxy, chlorine, bromine. and a substitutedacetoxy radical of the general structural for-.

mula:

t reuniopesticidal activity of these compounds, both the cis and.

trans isomers of the various compounds exhibiting substantially equallyhigh pesticidal activity.

Typical of the mono or half ester compounds of this invention are thecis and trans isomers of 'l-chloraceto'xy- 2-butene-4-ol;1-bromacetoxy-2-butene-4-ol; l-iodoacetoxy-2butene-4-ol, and similar.compounds wherein the hydroxyg'roup is replaced by a halogen such aschlorine 'iodoacetate. V

Allthe compounds covered by the general formula set Patented June 24,1958 or bromine as for example 1-bromacetoxy-2-butene-4- chloride, and1chloracetoxy-2-butene-4-bromide. Typical of the diesters are the cis andtrans isomers of 1,4-bisbromacetoxy-Z-buterie;1',4-bis-chloracetoxy-2-butene, and

1,4-iodoacetoxy-2-butene. Mixed esters include among others the cis andtrans isomers. of l-bromacetoxy-Z- 1-bromacetoxy-2-butene-4- butene-4chloracetate, and

forth above, both the cis and trans isomers, possess valuable fungicidalproperties. They can, therefore, be used: as active ingredients infungicidal preparations for therapeutic purposes or for technical uses,e. g. the preservation offoodstuif or books, articles of clothing orother objects to be preserved from the action of mold or'other fungi, orfor agricultural or horticultural purposes or the like. The compounds ofthis invention are particularly valuable. for use in agriculture orhorticulture, for they are systemic fungicides, i. e. the compounds ofthisinvention are found to enter the plant and pass throughout the plantby means of the plants internal sap. system. Thus, these fungicidesprotect plants from fungus from within, the compoundsentering the plant,for example by its roots along with nourishment absorbed by the plant.Compounds of my invention, evidencing particularly high fungistaticalactivity are the cis and trans isomers of 1,4-bis-bron1-acetoXy-Z-butene; 1-bromacetoxy-2-butene-4-ol, bromacetoxy2-butene-4-chloride.

Compounds ofthis invention, in addition to possessing'valuablefungicidal properties, have also been found to exhibit extremelyvaluable herbicidal and germicidal activity. For example, both the cisand trans isomers and lof l,4-bis-bromacetoxy-2-butene and1,4-bis-chloracetoXy- Z-butene exhibit herbicidal activity. In addition,cis-lbromacetoxy-2-butene-4-ol properties. a

The compounds of this invention may form an active ingredient of variousfungicidal, germicidal or herbicidal preparations such as by forming amixture of the active ingredient with a solid or liquid inert iarn'ermaterial, or if desired the active ingredient may be dissolved in asuitable solvent and the resulting solution used as such which may be Ireactant. It is remarkable that when the diol used as the startingmaterial is thus esterified with ,an equiacetic acid, such as' or formedinto a suitable emulsion with water. Also, the compoundso'f thisinvention may be combined with other fungicidal, herbicidal and/orgermicidal agents whereby composite or multipurpose preparations arethereby provided.

In preparing the mono or half ester compounds of this invention,

either cis or trans 2-butene-1,4-diol is esterified with aboutanequimolecular amount of a substituted acetic acid. compound selectedfrom the group consisting of chloracetic, brornacetic and iodoaceticacid, the esterification taking place in a suitable organicsolventmedium such as benzene. will be either the cis or trans isomerdepending upon which particular 2 -butene-l,4-diol isomer is utilized asa molecular amount .of substituted bromacetic acid, the esterificationthe land 4-positions only; of esterifications in the other .akes placein .one of of said positions.

The diestersareprepared in alomanner' similar'tolthat employed in thepreparation of the mono esters, however, at least about twicethemolecular equivalent of thediol of substituted acetic acid is employed.The

am; di le w l ba t the ew t e c .ortrans possesses valuable germicidalThe esterified product with the complete exclusion.

bromine isomer, depending upon w 'ch isomer of 2-butene-1,4-

diol is employed. The cis isomer of the diester can be changed to thetrans isomer by treatment of the cis isomer product with bromine in anorganic solvent, such as benzene, at room temperature, and thendistilling oil the bromine and solvent. Warming as by distillationfavors rearrangement.

Mixed esters. such as. 1 bl'OmailfiiOXiirblltQIle4Qih1bFr acetate.can-be preparedby esterifying. the mono. ester e. g.1-bromacetoxy-2vbutene-4-olwith. a. substituted acetic.

acid, suchlaschloracetic acid; in a suitabl egorganic solvent reactionmedium:

trans isomer which is a colorless crystalline solid M. P.

above. described. esterification lreactions'may be carried out at 'atemperature from about 70" totabout.

90 C., and. preferably at a temperature. not substantially aboveabout85C.

EXAMPLE V 'under vacuum at a temperature belowIabout 50 C., and

the residue is washed first with dilute sodium bicarbonate solution andthen with water until the washing. water' is neutral( In this manner,crude cis-l,4-bis-iodoacetoxy 2-butene is obtained; It is dried overcalcium chloride and purified by distillation in'a high vacuum. Theyield Thehydroxy grougo f. the monoor halt ester c anfbe replaced by ahalogen selected. from the group 2 consisting.

of chlorine andbromineflby halogenating'jja. l-substitntedacetoxy-2-butener4-ol compound a halogenating agent'such as thionylchloride or thionyl'bromide. For

' example, 1bromacetoxy-2-butene-4-chloride canbe pre.

pared by halogenating 1-bromacetoXy-Z-butene-4-ol with thionyl chloride.g

The compounds of the present. invention and "their preparation will bemore. clearly understood from a.consideration of the following specificexamples,'fwhich. are given for thepurpose of illustration only and arenot to be consideredas limiting the scope ofthe invention in anyway.f. gT

EXAMPLE I g 7 1 IIlOlGTOf cis'-2-butene l,4- diol and 2 moles ofbromacetic acidare dissolvedin 500cc. of benzene. Esterifi'cation occursspontaneously. course of the reaction is separated. whereby? theequilibrium ofthe'reaction'is'shiftedtowards the ester. formationandvirtually all' the diol; is esterified'. After the completion of thereaction the benzene is distilled ofii and theresidue iswashed firstwith dilute sodium bicar bonate solution" and then'with' water until theWashing water-is neutral. In this manner,crud'ecis.-l,4-bis-bromacetoxy-Z-butene is obtained. Itis driedover calciumchloride and purified by distillation in a high vacuum. The purifiedester is-a colorlessliquid ofB; P; l35f"136 C. under 0.005 mm. Hg. n =l.5-223. The yield" of purified esteris about 90% of r the theoreticalyield.

EXAMPLE n.

The water formed the lts index of" refraction is" acids present.

about 99% of cis-l-bromacetoxy-2-butene-4-chloride: is;

of purified ester is about 90% of the theoretical yield.

EXAMPLE VI Treatment of cis-l,4-bis iodoacetoxy-2=butene with bromine-inbenzene. at. roometemperature producesithe trans. isomer. 1

EXAMPLE VII 7.0 of dihydrofuran and 0 .5 g. of zinc dust areplaced'.

in. a-. flask equipped withv a reflux condenser. About 15.7 g. 0Lbrornacetyl chloride are added tothe flask in a plurality ofsmallamounts. After conclusion of the reaction,. the reaction mixture iswarmed. for about five minutes, and poured into a separatory funnelcontain.

ing. watervwith which the reaction mixture is: thoroughly mixed byagitation of the flask. Ethylene chloride is added to the flask, andthen a sodium bicarbonate S0111? tion is added to neutralize. excessacetic and hydrochloric About 22.5 g., representing a yield of obtainedby vacuum distillation. The product is a liquid,

B. P. 97 C. at 10 mm; Hg and index of. refraction iL =l.5059; V g M l II EXAMPLE VIII pletion of the reaction, the benzene is distilled off invacuo. The residue is washed with a concentrated potassium chloridesolution which dissolves any unreacted diol while the reaction productremains virtually undissolved. The cis-1-bromacetoxy-2-butene-4-ol soob- ;tained is dissolved in ether and the solution-is dried'ovenTreatment A of cis-1,4-bis-bromaceto ty 2 butene. with bromine 'in.benzene at-room temperature produces the EXAMPLE n1 1 mole ofcis-Z-butene- 1;,4-diol and "2j moles" of chlon' aceticacidfaredissolveddn 500cc. of benzene. Esterifi-.

' The watenforined in the cation occurs spontaneously; course of thereaction is separated whereby the equilibrium of the reaction isshiftedtowardsthe ester 'formation andvirtually all the diol isesterified. After the completion ofgthe reaction, the benzene isdistilledotf vacuum. .The purified ester isacolorless liquid of B. P.107-l08-C. under 0005 mm. Hg. Theyield of purified: ester is: about90%of the theoretical yield;

Treatment; ot CIS LA- lJIS-EMOI'Z CCtOXY-Z- butene with in benzene atroom temperature produces the trans isomer whichis a crystalline solid'of' P. 6-585 sodiumlsulfate. The yield is equal to the theoretical yieldcalculated. for bromacetic acid. The cis-l-bromaeetoxy- 2-butene-4-ol isa colorless liquid which on standing tends to assume a slightly brownishcolor. It boils at 7678 C. under 0.001 mm. Hg. Its index of refractionis I'l2 =1-5O23.

EXAMPLE IX In an analogous manner-as described in Example VIII, thetrans-l-bromaccto ry-2rbutene-4-ol' is obtained from trans-Z-butenel,l-dibl. The reaction product is solid at ordinary temperature. M. P;5960 C. Index of refraction r12 11502.

EXAMPLE X In; arn anner analogous to that described in Example VIII,trans-l-chloracetoxy-2-butene-4-ol is obtained from" '5trans-Z-buterie-lA-diol and chloracetic acid. The reaction product issolid at ordinary temperature.

EXAMPLE XII In an analogous manner as described in Example: VIII,cis-l-iodoacetoxy-2-butene-4-ol is obtained from cis-2- butene-l,4-dioland iodoacetic acid. The reaction prod-' uct is a liquid. EXAMPLE XIIIIn a manner similar to that described in Example VIII,

trans-l-iodoacetoxy-2-butene-4-ol is prepared from trans-2-butene-l,4-diol and iodoacetic acid. The reaction product is a solidat ordinary temperature.

EXAMPLE XIV poured into water and. the mixture is neutralized withsodium carbonate solution. The chloroform layer is then separated anddried over calcium chloride. After the evaporation of the chloroform invacuo there remains 22 g. of trans-1bromacetoxy-2-butene-4-chloride.This is a slightly yellowish, lachrym'atory liquid of B. P. 80 I C./0.0lmm. Hg, and index ofrefraction n 1 .4915.

EXAMPLE XV In an analogous manner as described in Example XIV,cis-l-bromacetoxy-2-butene-4-chlo1ide is prepared fromcis-l-bromacetoxy-2-butene-4-ol, the reaction product according toExample VIII. This is a liquid of B. P. 97 C./ mm. Hg and index ofrefraction n =l.5059.'

EXAMPLE XVI.

In an analogous manner as described in-Example XIV,trans-l-chloracetoxy-Z-butene-4-chloride is prepared from EXAMPLE XXI Ina manner similar to that described in Example XIV,cis-l-chloracetoxy-2-butene- I--bromide is obtained fromcis-1-chloracetoXy-2-butene-4-ol, the reaction product of Example X, andthionyl bromide. The product is a liquid at ordinary temperatures.

EXAMPLE XXII In a manner analogous to that described in Example XIV,trans-1-bromacetoxy-2-butene-4-bromide is obtained from,trans-l-brornacetoxy-2-butene-4-0l, the reaction productof Example IX,and thionyl bromide. The prod: net is a liquid at ordinary temperatures.a a

EXAMPLE XXIII In a manner analogous to that described in Example I XIV,cis-l-bromacetoxy-Z-butene4-brornide is obtained fromcis-1-bromacetoxy-2-butene-4-ol, the reaction product'of Example VIII,and'thionyl bromide. he product I is a liquid at ordinary temperatures.

trans-l-chloracetoxy-2-butene-4-ol, the reaction product uid at ordinarytemperatures.

' EXAMPLE XVII In ananalogous manner as described in ExampleXIV, cis-1chloracetoxy 2 butene-4-chloride is prepared fromcis-1-chloracetoxy-2-butene-4-ol, .the reaction product acaccording toExample XI. The reactionproduct a liqcording to Example X. The reactionproductis a liquid at ordinary temperature.

EXAMPLE XVIII In a manner similar to that described in Example XIV,cis-1iodoacetoxy-Z-butene-4-chloride is prepared fromcis-1-iodoacetoxy-2-butene-4-ol, the reaction product according toExample XII. The reaction product is a liquid at ordinary temperature.

EXAMPLE XIX EXAMPLE XX In an analogous manner as described in ExampleXIV, trans-l-chloracetoxy-2-butene-4-bromide is obtained from trans-lchloracetoxy-2-butene-4-ol, the reaction product of Example .XI, andthionyl bromide. The product is a liquid at ordinary temperature.

EXAMPLE XXIV I In an analogous manner as described in Example XIV,trans-1-iodoacetoxy-2-butene-4-bromide is prepared fromtrans-1-iodoacetoxy-2-butene-4-ol, the reaction product of Example XIII,and thionyl bromide. The product is a liquid at ordinary temperatures.

EXAMPLE XXV In ari analogous manner as described in Example XIV,cis-l-iodoacetoxy-2-butene-4-bromide is prepared fromcis-l-iodoacetoxy-2-butene-4-ol, the reaction product of Example XII,and thionyl bromide. The product is a liquid at ordinary temperatures.

The fungicidal activity of the products according to the invention wasascertained with Botrytis cinera Pers. .as a test fungus. Tests weremade both on solid and liquid substrates. The solid substrate wasprepared by boiling]; *4 g.'of agar-agar with 8 g. of maltose in 200 cc.of water for hours and adding 2 g. of peptone about 5 to 10 minutesbefore interrupting the heating. On being allowed to cool the mixtureremains a viscous liquid down to about 40 C., and jellifies on further.cooling to room temperature. The liquid substratewas prepared in the,

same way but without agar-agar.

The fungus was prepared for the test by transferring V a pure-culturemycelium into pure water by means of a platinum needle and thenfiltering the water through glass wool which retained the myceliu'm butallowed the spores to pass. The filtrate was diluted so as to containabout 7 500 spores'per drop.

Solid-substrate tests were made in Petri dishes of 5 cm. diameter with 5cc. of the agar-agar substrate each. Liquid tests were made in testtubes with 5 cc. of substrate solution each.

The fungicide compounds were used in solution, e. g. in water or in amixture of acetone and tertiary butyl alcohol. The concentration was1250000, calculated for the whole test medium. Inoculation was effectedwith 1 drop of the suspension of spores for each Petri dish or testtube.

It was found that the fungicides inhibited the growth of the fungus forperiods from 6 to 29 days, calculated from the beginning of growth on orin the substrate not admixed with the fungicide.

Results of these tests are set forth in Table I. In this table, theresults obtained with the compounds of this invention are compared withthose obtained with the known fungicides, salicylic acid andpentachlorophenol. The effectiveness of the compounds of the presentinvention is readily apparent by a comparison of the results obtained bythem with those obtained with pentachlorophenol, which is known to be anextremely effective fungicide.

Table 1 D ays Inhibition after Germination of Control (0oncentration'1f50,000) Isomer Formula Culture Medium Solid LiquidClGHzCOOOH2CH=CHCH2OCOOH2C1 4 ClCH2COOCHzCH=CHCH2OCOCHaCl 45CIOHICOOCHZCH=GHGH2OE 4 BPCH2GOO0H2CH=OHCH2OCOOH2BI' 6-12BI'OH2G,OOGH2OH=CHOHiOGOOHZB 10-12 BrCH2COOCH2CH=CHCH2C1 11-15BrOH2COOOHzOH=0110111011". 7 8-17 BrOHOOOOH1OH=OHGHOH 12-29 Standards Asstated-previously, the bromacetate butene-Z-derivatives exhibitgermicidal activity. For example, a Pe'tri plate containing nutrientagar-agar and one part in 10,000 of l bromacetoxy-2 butene-4-olprevented the growth of the organism Bacillus subtilis, when incubatedat 37 C. for a period of seven days. Similar results were obtained withl-brornacetoxy-2-butene 4-o1 in liquid medium under like conditions. Inboth instances, a similarsample not containing the germicide grewluxuriantly. Bisv 1,4-bromacetoay-2-butene was. tested as a germicide onbacteria obtainedfrorna' paper mill, and this compound was found toeffectively inhibit the growth of the bacteria at 10 p. p. m. in liquidmedium. a i J The bromacetate and chloracetate butene-2-derivatives ofthisinvention have been. found to possess valuable herbicidalproperties. As an example of such activity, ne'ttles have been killedwith a 0;l% aqueous solution of bromacetoxy 2-butene-4-ol andl-chloracetoxy-Z-butene- 4-01. Concentrated aqueous solutions of suchcompounds are also eflectiveherbicidal preparations. 1 a

Some modificationis possible in the selection of,tlie varioussubstituents and combinations thereof. as well'as in the particularprocedure employed in preparing the compounds without departing from thescopeofthe invention. l

I claim:

1. A. 1,4-substituted 2-butene derivative having the general structuralformula:

wherein X represents a substituent selected from the group consisting ofhydroxy, chlorine, bromine and a bromacetoxy group.

2. 1-bromacetoxy-2-butene-4-ol.

3. l4bromacetoxy-2-butene-4-chloride.

4. 1,4-bis-bromacetoxy-ZPbutene.

5. A process forthe preparation, of l-bromacetoxy-Z- bntene-4-ol which,comprises esterifying 'Z-butene-IA- diol with about anequimolecularamount of. bromaeetic acid.

6. A process for preparing the cis isomer of 1,4-bisbromacetoxy-2-butenewhich comprises esterifying. the

' cis isomer of 2-butene-1,4-diol with at least about twice themolecular equivalent of said diol of bromacetic acid.

7. A process for the preparation of the trans isomer of a1,4-bis-bromacetoxy-Z-bntene which comprises treatingcis-1,4-bis-bromacetOXy-Z-butene with bromine in an inert organicsolvent.

References Cited in the file of this patent UNITED STATES PATENTS2,366,667 Deebel Ian. 2, 1945 2,683,660 Schlesinger July 13; 19542,691,672 Brust Oct. 12, 1954 OTHER REFERENCES Arbuzovet'aL: Chem.Abstracts41 (1947), 3751 g-i. Fusco et al.: Gazz. Chim. ital 79 (1949),843-44. Wagner et al.,: Synthetic Organic Chemistry" (1953), p. 92.

1. A 1,4-SUBSTITUTED 2-BUTENE DERIVATIVE HAVING THE GENERAL STRUCTURALFORMULA: